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Glutamine is considered a non-essential nutrient since it can be synthesized from other materials. Normal demand for the amino acid is about 10 grams per day, which is what about 80 grams of mixed protein contains, although the daily requirement for protein for the average person is generally set at only about 50 grams. Perhaps the daily requirement should be set to 80 grams so that other amino acids are not being used to make additional glutamine.

In the normal course of things, the intestinal epithelium absorbs glutamine and uses some as fuel and converts some glutamine to proline for connective tissue repair and some to citrulline, which the kidneys convert to arginine (for NO synthesis and vasodilation; blood pressure control) and creatine (for muscle energy). The liver also uses glutamine to make glucose when blood sugar is falling below the threshold and of course also to make proline for connective tissue repair.

In critical care, the person is generally not consuming anywhere near enough protein to meet the needs, but the glutamine shortfall can be enormous because glutamine daily requirements can reach as high as 30 grams (240 grams of total mixed protein would contain about 30 grams of glutamine).

So right away the intestines are not getting enough glutamine to fuel themselves and one would predict a drop off in their two most basic functions, absorption and initial distribution of nutrients to the liver and synthesis of additional proline and citrulline. This is going to run the entire body down, the last thing one needs in critical care.

Consider metastatic cancer as an example of critical care: as cancer cells absorb glutamine at prodigious rates and convert it to glutamate and free fatty acids, and export both, the total demand for glutamine increases, and immune cells, which also use glutamine to fuel themselves, are weakened, and are weakened further by both glutamate and free fatty acids, and are less able to fight the cancer.

The free fatty acids excreted tend to increase insulin resistance, raising glucose baseline levels, which helps the cancer, as a prodigious consumer of glucose for fuel.

Is it possible that as proline levels fall off, connective tissue repair drops off, and it becomes easier for metastatic tumor cells to dissociate from the extracellular matrix and invade other tissues?

As creatine levels fall in response to low glutamine, does muscle wasting, already high, because they are being cannibalized to meet the body’s increased demands for protein, increase?

Do the conditions of cachexia not also decrease appetite, making the muscle wasting still more severe?